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            Gupta, Pramodkumar Pyarelal (Ed.)The GO DNA repair system protects against GC → TA mutations by finding and removing oxidized guanine. The system is mechanistically well understood but its origins are unknown. We searched metagenomes and abundantly found the genes encoding GO DNA repair at the Lost City Hydrothermal Field (LCHF). We recombinantly expressed the final enzyme in the system to show MutY homologs function to suppress mutations. Microbes at the LCHF thrive without sunlight, fueled by the products of geochemical transformations of seafloor rocks, under conditions believed to resemble a young Earth. High levels of the reductant H2and low levels of O2in this environment raise the question, why are resident microbes equipped to repair damage caused by oxidative stress? MutY genes could be assigned to metagenome-assembled genomes (MAGs), and thereby associate GO DNA repair with metabolic pathways that generate reactive oxygen, nitrogen and sulfur species. Our results indicate that cell-based life was under evolutionary pressure to cope with oxidized guanine well before O2levels rose following the great oxidation event.more » « less
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            Tight bosonic analogs of free-fermionic symmetry-protected topological phases, and their associated edgelocalized excitations, have long evaded the grasp of condensed-matter and AMO physics. In this paper, building on our initial exploration [Phys. Rev. Lett. 127, 245701 (2021)], we identify a broad class of quadratic bosonic systems subject to Markovian dissipation that realize tight bosonic analogs of the Majorana and Dirac edge modes characteristic of topological superconductors and insulators, respectively. To this end, we establish a general framework for topological metastability for these systems, by leveraging pseudospectral theory as the appropriate mathematical tool for capturing the nonnormality of the Lindbladian generator. The resulting dynamical paradigm, which is characterized by both a sharp separation between transient and asymptotic dynamics and a nontrivial topological invariant, is shown to host edge-localized modes, which we dub Majorana and Dirac bosons. Generically, such modes consist of one conserved mode and a canonically conjugate generator of an approximate phase-space translation symmetry of the dynamics. The general theory is exemplified through several representative models exhibiting the full range of exotic boundary physics that topologically metastable systems can engender. In particular, we explore the extent to which Noether’s theorem is violated in this dissipative setting and the way in which certain symmetries can nontrivially modify the edge modes. Notably, we also demonstrate the possibility of anomalous parity dynamics for a bosonic cat state prepared in a topologically metastable system, whereby an equal distribution between even and odd parity sectors is sustained over a long transient. For both Majorana and Dirac bosons, observable multitime signatures in the form of anomalously long-lived quantum correlations and divergent zero-frequency power spectral peaks are proposed and discussed in detail. Our results point to a paradigm for symmetry-protected topological physics in free bosons, embedded deeply in the long-lived transient regimes of metastable dynamics.more » « less
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            Abstract The GO DNA repair system protects against GC → TA mutations by finding and removing oxidized guanine. The system is mechanistically well understood but its origins are unknown. We searched metagenomes and abundantly found the genes encoding GO DNA repair at the Lost City Hydrothermal Field (LCHF). We recombinantly expressed the final enzyme in the system to show MutY homologs function to suppress mutations. Microbes at the LCHF thrive without sunlight, fueled by the products of geochemical transformations of seafloor rocks, under conditions believed to resemble a young Earth. High levels of the reductant H2and low levels of O2in this environment raise the question, why are resident microbes equipped to repair damage caused by oxidative stress? MutY genes could be assigned to metagenome assembled genomes (MAGs), and thereby associate GO DNA repair with metabolic pathways that generate reactive oxygen, nitrogen and sulfur species. Our results indicate that cell-based life was under evolutionary pressure to cope with oxidized guanine well before O2levels rose following the great oxidation event.more » « less
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            Photoredox-mediated metal-free ring-opening metathesis polymerization (MF-ROMP) is a convenient metal-free method to produce a variety of ROMP polymers. Transitioning MF-ROMP from a batch to a continuous flow process has yet to be demonstrated and could potentially benefit production efficiency, safety, and modularity of reaction conditions. We designed and evaluated continuous flow and droplet flow setups and compared the results for MF-ROMP across a short series of common monomers. By using the droplet flow reactor setup, we achieved flow conversions comparable to that of batch, and circumvented issues with diffusion-limited mixing and air exposure.more » « less
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            Phenol-soluble modulins (PSMs) are peptide-based virulence factors that play significant roles in the pathogenesis of staphylococcal strains in community-associated and hospital-associated infections. In addition to cytotoxicity, PSMs display the propensity to self-assemble into fibrillar species, which may be mediated through the formation of amphipathic conformations. Here, we analyze the self-assembly behavior of two PSMs, PSMα3 and PSMβ2, which are derived from peptides expressed by methicillin-resistant Staphylococcus aureus (MRSA), a significant human pathogen. In both cases, we observed the formation of a mixture of self-assembled species including twisted filaments, helical ribbons, and nanotubes, which can reversibly interconvert in vitro. Cryo–electron microscopy structural analysis of three PSM nanotubes, two derived from PSMα3 and one from PSMβ2, revealed that the assemblies displayed remarkably similar structures based on lateral association of cross-α amyloid protofilaments. The amphipathic helical conformations of PSMα3 and PSMβ2 enforced a bilayer arrangement within the protofilaments that defined the structures of the respective PSMα3 and PSMβ2 nanotubes. We demonstrate that, similar to amyloids based on cross-β protofilaments, cross-α amyloids derived from these PSMs display polymorphism, not only in terms of the global morphology (e.g., twisted filament, helical ribbon, and nanotube) but also with respect to the number of protofilaments within a given peptide assembly. These results suggest that the folding landscape of PSM derivatives may be more complex than originally anticipated and that the assemblies are able to sample a wide range of supramolecular structural space.more » « less
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